Alternating ring-opening metathesis polymerization

ABSTRACT

The invention relates to the field of polymers and olefin polymerization, and more specifically olefin metathesis polymerization. The invention provides regioregular alternating polymers and methods of synthesizing such polymers. To demonstrate, polymers were synthesized and modified with a FRET pair (Trp/Dansyl) post-polymerization.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a 371 of International application numberPCT/US2014/047674 filed Jul. 22, 2014, which claims the benefit ofpriority to U.S. Application No. 61/857,189, filed Jul. 22, 2013, andU.S. Application No. 61/858,811, filed Jul. 26, 2013, which areincorporated herein by reference in their entireties

STATEMENT OF INTEREST

This invention was made with government support under grant numbersHD038519 and GM097971 awarded by the National Institutes of Health andgrant number DBI1039771 awarded by the National Science Foundation. Thegovernment has certain rights in the invention.

FIELD OF THE INVENTION

The invention relates to the field of polymers and olefinpolymerization, and more specifically olefin metathesis polymerization.

BACKGROUND

Copolymers are employed in a wide range of materials, ranging from bulkplastics to specialized coatings, pharmaceutical compositions, andbiomedical and electronic devices. Among the most commonly used areblock copolymers, which often rely on phase separation of the two blocksfor their functional properties, for example in drug deliverynanoparticles, and random copolymers, which incorporate two or morefunctional moieties that act co-operatively, for example in organiclight emitting diodes. Regularly alternating polymers allow forcontrolled positioning of functional substituents, but they aredifficult to access synthetically.

Regioregular alternating polymers (for example, SAN,styrene-acrylonitrile, an alternating copolymer used in plastics) aregenerally synthesized by radical polymerization with kinetic control ofalternation in the polymerization reaction.^(1,2) Recently, ring openingmetathesis polymerization (ROMP) and ring opening insertion metathesispolymerization (ROIMP)³ have been employed to synthesize alternatingpolymers: Ilker, M. F.; Coughlin, E. B. Macromolecules 2002, 35, 54-58;Choi, T. L.; Rutenberg, I. M.; Grubbs, R. H. Angewandte Chemie-Intl.Ed., 2002, 41, 3839-3841; PCT publication WO 03/070779.

The existing methods of formation of alternating polymers are limited,and there remains a need for new and more structurally diversesubstrates and polymers. The present invention provides substrate andcatalyst combinations that can generate a wider range of alternatingpolymers, having a range of diverse properties.

Herein we address both, the limitation of the NB/COE ROMP, i.e. theformation of COE homoblocks, as well as the intramolecular chaintransfer of current AROMP by utilizing CBE/CH monomers containing theDAN-PDI pair to achieve perfectly alternating copolymers. We show thatthese polymers exhibit a higher intensity charge-transfer absorbancethan analogous poly(NB-alt-COE) polymers.

BRIEF DESCRIPTION OF THE INVENTION

The invention provides a method for producing an alternating ABcopolymer comprising the repeating unit Ia, Ib, or Ic:

in which the A monomer is derived from a cyclobutene 1-carboxyl or1-carbonyl derivative III, and the B monomer is derived from acyclohexene derivative II.

The method comprises contacting the cyclohexene derivative II with thecyclobutene derivative III in the presence of an olefin metathesiscatalyst. This polymerization method enables the facile preparation ofamphiphilic and bifunctional alternating polymers from simple andreadily available starting materials.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows chemical structures of monomers and catalyst (box) used forAROMP.

FIG. 2 shows partial UV-Vis spectra of the charge-transfer region inchloroform. a) Comparison of alternating copolymers. Upper trace=3 mMpoly(1-alt-5)₁₀, middle trace=100 μM poly(1-alt-5)₁₀, lower trace=3 mMpoly(NB-alt-COE)-block-poly(COE). b) Plot of charge-transfer absorbanceversus concentration of poly(1-alt-5)₁₀.

FIG. 3 depicts the ¹H-NMR spectrum of11-(5-(hexyloxy)naphthalen-1-yloxy)undecyl cyclobut-1-enecarboxylate (1)

FIG. 4 depicts the ¹³C-NMR spectrum of11-(5-(hexyloxy)naphthalen-1-yloxy)undecyl cyclobut-1-enecarboxylate (1)

FIG. 5 depicts the ¹H-NMR spectrum of 2,5-dioxopyrrolidin-1-ylcyclohex-3-enecarboxylate (3).

FIG. 6 depicts the ¹³C-NMR spectrum of 2,5-dioxopyrrolidin-1-ylcyclohex-3-enecarboxylate (3).

FIG. 7 depicts the ¹H-NMR spectrum of poly(1-alt-2)₅.

FIG. 8 depicts the ¹H-NMR spectrum of poly(1-alt-3)₁₀.

FIG. 9 depicts the ¹H-NMR spectrum of poly(1-alt-5)₁₀.

FIG. 10 depicts a partial ¹H-NMR spectrum of a) 1; b) poly(1-alt-2)₅;and c) 2.

FIG. 11 depicts GPC traces of alternating copolymers. a) poly(1-alt-2)₅;b) poly(1-alt-5)₁₀. Molecular weights and polydispersity indices weremeasured using UV detection with CH₂Cl₂ as the eluent and a flow rate of0.700 mL/min on an American Polymer Standards column (Phenogel 5μ MXLGPC column, Phenomenex). All GPCs were calibrated using poly(styrene)standards and carried out at 30° C.

FIG. 12 depicts fluorescence of the polymers. a) The emission spectra ofpoly(3′-alt-4-DH)_(n) and poly(3′-Trp-alt-4-DH). (1.2 μM in THF) excitedat characteristic wavelengths of tryptophan (284 nm) and dansylfluorophore (335 nm). b) Plot of charge-transfer absorbance ofpoly(3′-alt-4-DH)_(n) and poly(3′-Trp-alt-4-DH)_(n) versus concentrationranging from 0.2 μM and 3 μM. c) Concentration dependence offluorophores without the backbone showed no emission difference betweena two fluorophore mixture and dansyl fluorophore alone.

DETAILED DESCRIPTION OF THE INVENTION

The invention provides a method for producing an alternating ABcopolymer comprising the repeating unit Ia, Ib or Ic:

which comprises contacting an olefin of structure II with a cyclobuteneof structure III

in the presence of an olefin metathesis catalyst. It will be understoodthat asterisk (*) at the end of a repeating unit can be interpreted asthe point of attachment and may be terminated with a functional group asis known in the art. In the above structures, R may be, but is notlimited to, H, C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₃-C₈ cycloalkyl,heterocyclyl, aryl, C₁-C₂₀ alkoxy, C₁-C₂₀ alkenyloxy, C₃-C₆cycloalkyloxy, aryloxy, heterocyclyloxy, C₁-C₂₀ alkylamino, C₁-C₂₀alkenylamino, C₃-C₈ cycloalkylamino, heterocyclylamino, or arylamino andmay be optionally substituted with up to three substituents selectedfrom halo, CN, NO₂, oxo, alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl,aryl, and a heterocyclic group. In certain embodiments, the repeatingunit, n, is between 2 and 20. Each substituent R¹ through R⁶ mayindependently be, but is not limited to, H, aldehyde, C₁-C₂₀ alkyl,C₂-C₂₀ alkenyl, C₃-C₆ cycloalkyl, aryl, heterocyclyl, C₁-C₂₀ alkoxy,C₁-C₂₀ acyloxy, C₂-C₂₀ alkenyloxy, C₃-C₆ cycloalkyloxy, aryloxy,heterocyclyloxy, C₁-C₂₀ alkylamino, C₂-C₂₀ alkenylamino, C₃-C₈cycloalkylamino, heterocyclylamino, arylamino, or halogen; with theproviso that any carbon-carbon double bonds in R or in R¹ through R⁶ areessentially unreactive toward metathesis reactions with the catalyst. Itwill be also understood that adjacent substitutions of R¹-R⁶ may betaken together to form a 5- to 7-membered ring which may be optionallysubstituted with up to three substituents selected from halo, CN, NO₂,oxo, alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, aryl, and aheterocyclic group. In certain embodiments, A may be, but is not limitedto C₂-C₂₀ alkyl. In another embodiment, A is C₈-C₁₂ alkyl. In anotherembodiment, R¹ through R⁶ may be independently be C(O)NH—C₁-C₂₀alkyl-N(R⁷)(R⁸). Each R⁷ and R⁸ are independently selected from H, C₂-C₆alkyl, cycloalkyl, cycloalkenyl, alkyl-O-alkyl, alkyl-O-aryl, alkenyl,alkynyl, aralkyl, aryl and a heterocyclic group; or R⁷ and R⁸ may betaken together with the nitrogen to which they are attached form a 5- to7-membered ring which may optionally contain a further heteroatom andmay be optionally substituted with up to three substituents selectedfrom halo, CN, NO₂, oxo, alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl,aryl, and a heterocyclic group.

By way of example, suitable cyclohexene and cyclobutene species includebut are not limited to the following:

It will be understood that olefins in the substituents should beessentially unreactive with the metathesis catalyst under the reactionconditions, so that the metathesis polymerization involves thecyclobutene and cyclohexene double bonds exclusively, or nearly so.Generally, any carbon-carbon double bonds in R or in R¹ through R⁶should be trisubstituted or tetrasubstituted, or otherwise renderedunreactive with the catalyst.

Aryl, as used herein, includes but is not limited to optionallysubstituted phenyl, naphthyl, anthracenyl, and phenanthryl groups.Heterocycle and heterocyclyl refer to monocyclic and fused polycyclicheteroaromatic and heteroaliphatic ring systems containing at least oneN, O, S, or P atom. Aryl and heterocyclic groups may contain from 1 to60 carbon atoms, and may range from furan, thiophene, and benzene tolarge chromophores such as phthalocyanines and fullerenes. For someapplications, aryl and heterocyclic groups will preferably contain from1 to 20 carbon atoms.

It will be apparent that alkyl, alkenyl, cycloalkyl, heterocyclyl, acyl,and aryl moieties in the substituents R and R¹ through R⁶ may besubstituted with functional groups known to be compatible with thecatalyst. Examples include, but are not limited to, C₁-C₄ acyl, acyloxy,acylamino, amido, aryloxy, alkoxy and alkylthio groups; halogens;protected amino groups such as BocNH— and FmocNH—; protected hydroxygroups such as TMSO—, BzO—, and BnO—; and protected carboxyl groups suchas —CO₂-t-Bu and —CO₂Bn. Accordingly, the terms alkyl, alkenyl,cycloalkyl, acyl, aryl, and heterocyclyl as used herein encompass suchsubstituents.

The method may be used to prepare block copolymers as well, in which oneblock comprises the repeating units Ia, Ib, or Ic; the proportion ofalternating and block copolymer regions in the polymer being dependentupon the catalyst and substrate. The catalyst may be any olefinmetathesis catalyst known in the art, such as those disclosed in WO03/070779. It is preferably an alkylidene ruthenium complex, and morepreferably a complex of formula (L)2(L′)X₂Ru═CHR′, wherein R′ may be,for example, H, C₁-C₁₀ alkyl, C₂-C₁₀ alkenyl, C₃-C₆ cycloalkyl, or aryl.The ligand L is typically a trialkyl phosphines, triarylphosphines,tri(cycloalkyl)phosphines, pyridines, aryl, wherein aryl is optionallysubstituted with a halogen. L′ is a second ligand, and may be a trialkylphosphine, triarylphosphine, tri(cycloalkyl)phosphine, or a pyridine. L′may also be an imidazolin-2-ylidine carbene of formula IV:

wherein R⁹ may be selected from the group, but is not limited to a C₁-C₆alkyl group or aryl. In certain embodiments, X is a halogen orpseudohalogen such as F, Cl, Br, NO₃, CF₃, or CF₃COO⁻.

In certain embodiments, L is a pyridine, optionally 3-bromopyridine; andL′ is an imidazolin-2-ylidine carbene. In another embodiment, R⁹ ispreferably mesityl, 2-methylphenyl, 2-ethylphenyl, 2-isopropylphenyl,2,3-diisopropylphenyl, 2, 6-difluorophenyl, or 3,5-di-t-butylphenyl.

The invention also provides the following polymer comprising therepeating unit Ia, Ib, or Ic.

The polymers of the present invention may be prepared according to therepresentative Schemes 1 through 3.

The target monomers and catalyst are shown in FIG. 1. The syntheses ofthe side-chains are in close analogy to published methods.⁴ Based onprevious studies,⁵ synthetic route 1 (Scheme 1) was first investigatedfor the alternating copolymerization of the DAN and PDI functionalizedCBE and CH monomers, respectively. This route successfully affordedpoly(1-alt-2)₅. However, longer polymerization times were required dueto the significant steric hindrance presented by the side-chain units.This resulted in a decrease in the rate of polymerization inhibiting theformation of higher molecular weight polymers.

To minimize steric hindrance and to achieve a higher degree ofpolymerization, a revised synthetic route was applied using DAN-CBE 1and a cyclohexene functionalized with N-hydroxysuccinimide (NHS)(compound 3) for AROMP (Scheme 2). The NHS group is less bulky than thePDI, and is not reactive during the polymerization. The PDI ester canthen be formed via a post-polymerization functionalization strategy togenerate poly(1-alt-5)₁₀. This modified route not only allowed for ahigher degree of polymerization, but also provided an alternativestrategy for the incorporation of the PDI moiety.

Previous studies on poly(CBE-alt-CH)_(n) revealed signals in the ¹H NMRspectrum corresponding to concentration-independent intramolecularbackbiting of the enoic ruthenium carbene on the unhindereddisubstituted alkenes in the polymer backbone.⁵ As a result,polydispersity indices of unfunctionalized poly(CBE-alt-CH)_(n) werelarger than 2 and a significant fraction of the polymer was cyclic. Inour case, poly(1-alt-2)₁₀ and poly(1-alt-5)₁₀ did not show any protonresonance signals due to backbiting, had PDIs lower than 1.3, anddisplayed a monomodal distribution. We hypothesize that backbiting isinhibited by the increased steric hindrance at the enoic carbene anddisubstituted alkene in combination with the restricted flexibility ofthe polymer backbone upon modification with larger substituents. As aconsequence, longer AROMP copolymers were obtained than previouslyreported.

We designed a new set of cyclobutene derivatives as monomers withbicyclic structures which are very strained and can incorporate ringsinto the polymeric backbone.⁵ Therefore we utilized functional group Brcontaining bicyclo[4.2.0]oct-7-ene-7-carboxylate and aldehyde containingcyclohexene as the AROMP pair which provides a facile approach toprepare long and completely alternating copolymers with orthogonalfunctional groups. Post-polymerization modification of Br with an azidegroup allows click-chemistry while the aldehyde can be coupled to ahydrazide to introduce fluorophores which are not compatible with AROMPreactions.

The alternating copolymers were further modified according to Scheme 4to crosslink with dansyl hydrazide (DH) and form poly(3′-alt-4-DH)_(n);it was coupled with Boc-Trp-alkyn to form poly(3′-Trp-alt-4)_(n); bothfluorophores were introduced in a one-pot reaction to providepoly(3′-Trp-alt-4-DH)_(n).

UV-Vis spectroscopy was utilized to investigate the charge-transferbetween the side-chains of the alternating copolymers in solution. TheUV-Vis spectrum of poly(1-alt-5)₁₀ (3 mM in chloroform) shows acharge-transfer absorbance at the characteristic wavelength (FIG. 2alight blue trace) indicating that the side-chains are able to favorablyorient to transfer energy in this system. A concentration study from 3mM to 100 μM was carried out to determine if these interactions occurinter- or intramolecularly. As shown in FIG. 2a , the charge-transferabsorbance signal was persistent even at low concentrations. Moreover,the absorbance followed Beer-Lambert behavior based on the concentrationof polymer (FIG. 2b ), which demonstrated that the charge-transfer isintramolecular. Additionally, the aromatic signals in the ¹H NMRspectrum of poly(1-alt-5)₁₀ are shifted upfield in comparison to theindividual monomers (FIG. S10). These shifts further indicate the pi-pistacking of the donor-acceptor aromatic units, and are consistent withsimilar shifts previously reported for partially-folded polymers.⁶

We compared the charge-transfer absorbance of the functionalizedpoly(CBE-alt-CH)s to the previously reported functionalizedpoly(NB-alt-COE)-b-COE.⁴ As shown in FIG. 2, poly(1-alt-5)₁₀ exhibits ahigher charge-transfer absorbance intensity in comparison to the NB/COEpolymers at the same concentration, which indicates that the newpoly(1-alt-5)₁₀ polymers more favorably align the aromatic units of thedonor and acceptor moieties.

In conclusion, we have demonstrated the AROMP of CBE and CH monomerscontaining bulky DAN/PDI side-chains. We attribute inhibition ofbackbiting to the steric hindrance provided by bulky side-chains aroundthe carbene and the polymer alkenes. UV-Vis spectroscopic analysis showsa charge-transfer absorbance signal for the perfectly alternatingcopolymers signifying the alignment of the side-chains. The new polymersdemonstrate an enhancement of charge-transfer in comparison topreviously studied polymers, indicating that the sequence specificity inalternating CBE-CH copolymers provides efficient energy transfer.

Throughout this application, various publications, reference texts,textbooks, technical manuals, patents, and patent applications have beenreferred to. The teachings and disclosures of these publications,patents, patent applications and other documents in their entireties arehereby incorporated by reference into this application to more fullydescribe the state of the art to which the present invention pertains.However, the citation of a reference herein should not be construed asan acknowledgement that such reference is prior art to the presentinvention.

It is to be understood and expected that variations in the principles ofinvention herein disclosed can be made by one skilled in the art and itis intended that such modifications are to be included within the scopeof the present invention. The following Examples further illustrate theinvention, but should not be construed to limit the scope of theinvention in any way.

EXAMPLES

11-((5-(hexyloxy)naphthalen-1-yl)oxy)undecan-1-ol.11-((5-(hexyloxy)naphthalen-1-yl)oxy)undecan-1-ol was synthesized from1,5-dihydroxynapthalene, 1-bromo-hexane, and 11-bromo-1-undecanol in twoconsecutive steps using a catalytic Williamson ether synthesis.⁴

Cyclobut-1-enecarboxylic acid. Cyclobut-1-enecarboxylic acid wasprepared according to the procedure for the preparation of3,3-dimethylcylobutene carboxylic acid as described by Campbell et al.⁷and modified as previously reported.⁵ ¹H-NMR (400 MHz, CDCl₃) δ 10.23(bs, 1H), 6.94 (t, J=1.2 Hz, 1H), 2.76 (t, J=3.2 Hz, 2H), 2.51 (td,J=3.2 Hz, 1.2 Hz, 2H). ¹³C NMR (100 MHz, CDCl₃) δ 167.5, 150.1, 138.4,29.1, 27.5.

11-(5-(hexyloxy)naphthalen-1-yloxy)undecyl cyclobut-1-enecarboxylate(1). To a solution of cyclobut-1-enecarboxylic acid (190 mg, 1.94 mmol)and dicyclohexylcarbodiimide (DCC) (417 mg, 2.04 mmol) in CH₂Cl₂ (10 mL)stirred at 0° C. for 30 minutes,11-((5-(hexyloxy)naphthalen-1-yl)oxy)undecan-1-ol (400 mg, 0.97 mmol)and a catalytic amount of dimethylaminopyridine (DMAP) were added. Themixture was allowed to warm to rt over 12 h. CH₂Cl₂ was evaporated underreduced pressure and the crude product was purified by flashchromatography (1:1/hexanes:CH₂Cl₂) to afford 1 in 35% yield: ¹H NMR(600 MHz, CDCl₃) δ 7.86 (d, J=8.2 Hz, 2H), 7.36 (t, J=7.6 Hz, 2H), 6.84(d, J=7.2 Hz, 2H), 6.80 (s, 1H), 4.10 (m, 6H), 2.74 (s, 1H), 2.47 (s,1H), 1.93 (d, J=6.3 Hz, 2H), 1.67 (d, J=6.4 Hz, 1H), 1.58 (d, J=5.7 Hz,2H), 1.36 (d, J=45.9 Hz, 8H), 0.94 (s, 2H). ¹³C NMR (126 MHz, CDCl₃) δ162.3, 154.6, 154.6, 146.1, 146.1, 138.8, 126.7, 124.9, 113.9, 113.9,105.1, 68.0, 64.2, 64.2, 33.9, 32.7, 31.6, 29.5, 29.4, 29.4, 29.4, 29.3,29.2, 29.0, 28.7, 28.6, 25.9, 25.8, 22.6, 14.0.

Cyclohex-3-en-1-ylmethyl3-(6-decyl-1,3,5,7-tetraoxo-6,7-dihydropyrrolo[3,4-f]isoindol-2(1H,3H,5H)-yl)propanoate (2). Monomer 2 was prepared frompyromellitic dianhydride and cyclohex-3-en-1-ylmethyl 3-aminopropanoateby methods known in the art.⁴

2,5-dioxopyrrolidin-1-yl cyclohex-3-enecarboxylate (3).3-Cyclohexene-1-carboxylic acid (100 mg, 0.79 mmol),N-hydroxysuccinimide (100 mg, 0.87 mmol), and ethyl, dimethylaminopropylcarbodiimide hydrochloride (EDC.HCl) (182 mg, 0.95 mmol) were dissolvedin CH₂Cl₂ and cooled in an ice bath. Then DIEA was added to adjust thepH to 8-9. The reaction was stirred for 16 h and washed with 5% Na₂CO₃(50 mL). The organic phase was dried and condensed, followed by flashchromatography, eluted with 100% CH₂Cl₂ to yield a white solid in 80%yield: ¹H NMR (600 MHz, CDCl₃) δ 5.88-5.44 (m, 2H), 3.01-2.80 (m, 1H),2.76 (s, 4H), 2.42-2.22 (m, 2H), 2.17-1.92 (m, 3H), 1.90-1.62 (m, 1H).¹³C NMR (100 MHz, CDCl₃) δ 170.6, 169.2, 126.6, 124.0, 36.6, 26.9, 25.4,24.6, 23.6.

2-(6-aminohexyl)-6-decylpyrrolo [3,4-f]isoindole-1,3,5,7(2H,6H)-tetraone(5). Compound 5 was synthesized from pyromellitic dianhydride,decylamine, and N-Boc-1,6-hexanediamine according to methods known inthe art.⁴

2-Bromoethyl bicyclo[4.2.0]oct-7-ene-7-carboxylate (6).Bicyclo[4.2.0]alkene carboxylic acid was obtained according to theliterature with a yield of 62%.^(8, 9, 21) The acid (500 mg, 3.3 mmol)was dissolved in 5 mL of CH₂Cl₂ and was cooled in an ice bath whenoxalyl chloride (5 mL) was added. The reaction was stirred for 30 minfollowed by evaporation to yield bicyclo[4.2.0]oct-7-ene-7-carbonylchloride as off white oil. 2-Bromoethanol (1.2 mg, 10 mmol), EDC.HCl(630 mg, 3.3 mmol), DIPEA (425 mg, 3.3 mmol) were mixed with the acylchloride oil in 20 mL of CH₂Cl₂. The mixture was stirred for 16 h andwas washed with 5% NaHCO₃ (3×), 1N HCl (3×) and brine (2×) sequentiallyand dried over anhydrous MgSO₄. The solvent was filtered and removed byevaporation. The crude was subjected to flash silica chromatography(30:70/hexane:CH₂Cl₂) to yield 3 (590 mg, 70%): ¹H NMR (500 MHz,CD₂Cl₂): δ 6.91 (d, J=1.1 Hz, 1H), 4.46 (m, 2H), 3.60 (t, J=6.1 Hz, 2H),3.04 (dd, J=10.3 Hz, J=5.6 Hz, 1H), 2.77 (td, J=5.6 Hz, J=1.1 Hz, 1H),1.74 (m, 3H), 1.55-1.38 (m, 5H). ¹³C NMR (100 MHz, CDCl₃) 161.4, 151.6,141.0, 63.0, 40.0, 38.4, 28.6, 23.4, 18.8, 18.2. HRMS (ESI) calcd. forC₁₁H₁₅BrO₂ [M+H]⁺ 258.0255, found 258.0248.

Boc-Trp-OH. Tryptophan (1.00 g, 4.90 mmol) was dissolved in saturatedNaHCO₃ aqueous solution and cooled in an ice bath. Boc anhydride (2.14g, 9.80 mmol) was dissolved THF and added dropwise into the tryptophansolution and the reaction was stirred for 10 h. The organic solvent wasremoved by evaporation and the remaining aqueous solution was washedwith CH₂Cl₂ (3×20 mL). The water layer was acidified with 1N HCl to pH=2and was extracted with CH₂Cl₂ (3×20 mL). The organic layer was driedover MgSO₄. The solvent was filtered and removed by evaporation to yieldBoc-Trp-OH as a white solid. It was recrystallized in ethyl acetate withhexane and used without further purification.

Boc-Trp-alkyn. BocTrp-OH (500 mg, 1.64 mmol), propagyl amine (82.1 mg,1.49 mmol), EDC.HCl (347 mg, 1.80 mmol) and DIPEA (233 mg, 1.80 mmol)were mixed in THF. The reaction was stirred for 10 h and THF was removedby evaporation. The residue was dissolved in CH₂Cl₂ and washedsequentially with 5% NaHCO₃ (3×), 1N HCl (3×) and brine (2×) and driedover anhydrous MgSO₄. The solvent was filtered and removed byevaporation and the crude was subjected to flash silica chromatography(2% MeOH in CH₂Cl₂) to yield Boc-Trp-alkyn (390 mg, 78%). ¹H NMR (700MHz, CDCl₃) 8.28 (s, 1H), 7.66 (d, J=7.5 Hz, 1H), 7.38 (d, J=8.1 Hz,1H), 7.25-7.20 (m, 1H), 7.18-7.13 (m, 1H), 7.06 (s, 1H), 6.12 (s, 1H),5.18 (s, 1H), 4.48 (s, 1H), 3.93 (s, 2H), 3.32 (s, 1H), 3.21 (s, 1H),2.17 (s, 1H), 1.44 (s, 9H). ¹³C NMR (176 MHz, CDCl₃) 171.5, 155.5,136.2, 127.5, 123.3, 122.3, 119.8, 118.8, 111.3, 110.4, 80.3 79.16,71.5, 55.0, 29.1, 28.3. ESI (M/Z) [M+H]⁺ 341.2.

General Procedure for AROMP

The NMR tube was evacuated under high vacuum for 15 min, and then waspurged with N₂ gas for another 15 min. Under an N₂ atmosphere, asolution of monomer A in CD₂Cl₂ (300 μL) was added to the NMR tube. Thena solution of catalyst (H₂IMes)(3-Br-Py)₂(Cl)₂Ru═CHPh in CD₂Cl₂ (300 μL)was added to the NMR tube. After complete mixing of the solution, theNMR tube was spun for 60 min at an elevated temperature 37° C. until theprecatalyst had reacted as can be observed by disappearance of rutheniumalkylidene proton at 19 ppm. Monomer B (cyclohexene derivative) inCD₂Cl₂ (100 μL) was added to the NMR tube. The reaction was quenched in8 h with ethyl vinyl ether (50 μL) and the resulting solution wasstirred for another 1 h.

poly(1-alt-2)₅. The reaction was monitored by ¹H NMR. The NMR tube wasevacuated under high vacuum for 15 min, and then was purged with N₂ gasfor another 15 min. Under an N₂ atmosphere, a solution of monomer 1(29.6 mg, 0.060 mmol) in CD₂Cl₂ (300 μL) was added to the NMR tube. Thena solution of catalyst (H₂IMes)(3-Br-Py)₂(Cl)₂Ru═CHPh (4, 5.3 mg, 6.0μmol) in CD₂Cl₂ (300 μL) was added to the NMR tube. After completemixing of the solution, the NMR tube was spun for 60 min at an elevatedtemperature 37° C. until the precatalyst had reacted as can be observedby disappearance of ruthenium alkylidene proton at 19 ppm. Monomer 2(19.5 mg, 0.030 mmol) in CD₂Cl₂ (100 μL) was added to the NMR tube. Thereaction was quenched in 8 h with ethyl vinyl ether (50 μL) and theresulting solution was stirred for another 1 h. The mixture wascondensed to give a dark brown oil which was further purified by columnchromatography (100:1/CH₂Cl₂:MeOH (methanol)) to yield an orange solidin 55% yield. ¹H NMR (600 MHz, CDCl₃) δ 8.26-7.92 (m, 8H), 7.83-7.74 (m,10H), 7.42-7.20 (m, 10H), 6.93-6.62 (m, 15H), 5.66-5.17 (m, 8H),4.30-3.91 (m, 41H), 3.72 (m, 16H), 3.41-3.03 (m, 6H), 2.65-1.02 (m,382H), 0.99-0.62 (m, 34H). Mn^(cal)=5748, Mn^(GPC)=3291, Mw^(GPC)=4252,PDI=1.29.

poly(1-alt-5)₁₀. The reaction was monitored by ¹H NMR. The NMR tube wasevacuated under high vacuum for 15 min, and then was purged with N₂ gasfor another 15 min. Under an N₂ atmosphere, a solution of monomer 1(29.6 mg, 0.060 mmol) in CD₂Cl₂ (300 μL) was added to the NMR tube. Thena solution of catalyst (H₂IMes)(3-Br-Py)₂(Cl)₂Ru═CHPh (4, 5.3 mg, 6.0μmol) in CD₂Cl₂ (300 μL) was added to the NMR tube. After completemixing of the solution, the NMR tube was spun for 60 min at 25° C. untilthe precatalyst had reacted as can be observed by disappearance ofruthenium alkylidene proton at 19 ppm. Monomer 3 (26.8 mg, 0.120 mmol)in CD₂Cl₂ (100 μL) was added to the NMR tube. The reaction was quenchedin 6 h with ethyl vinyl ether (50 μL) and the resulting solution wasstirred for another 1 h. The mixture was condensed to give a dark brownoil which was further purified by column chromatography(100:1/CH₂Cl₂:MeOH) to yield an orange solid in 75% yield. ¹H NMR (600MHz, CDCl₃) δ 7.84 (m, 20H), 7.32 (m, 20H), 6.98-6.56 (m, 30H), 5.33 (m,13H), 4.11 (s, 3H), 292-1.25 (m, 366H), 0.95 (m, 30H). The resultingpolymer poly(1-alt-3)₁₀ (27.2 mg, 3.7 μmol) was dissolved in dry THF andcooled in an ice bath. EDC.HCl (7.1 mg, 37 μmol), DIEA (9.7 mg, 74μmol), and2-(6-aminohexyl)-6-decylpyrrolo[3,4-f]isoindole-1,3,5,7(2H,6H)-tetraone(5) (34 mg, 74 μmol) were added. The mixture was stirred for 2 days andthen filtered, followed by column chromatography (5:95/acetone/CH₂Cl₂)to yield an orange solid in 20% yield. ¹H NMR (600 MHz, CDCl₃) δ8.26-7.92 (m, 9H), 7.80 (dd, J=14.4, 6.1 Hz, 20H), 7.42-7.18 (m, 20H),6.93-6.62 (m, 30H), 5.66-5.17 (m, 12H), 4.30-3.91 (m, 59H), 3.72 (dd,J=14.7, 7.1 Hz, 15H), 3.41-3.03 (m, 6H), 2.65-0.99 (m, 545H), 0.99-0.62(m, 86H). Mn^(Cal)=10948, Mn^(GPC)=7966, Mw^(GPC)=10221, PDI=1.28.

Poly(3-alt-4)_(n). Under an N₂ atmosphere, 6 (61.8 mg, 0.24 mmol) and G1(5.3 mg, 0.006 mmol) were mixed in CD₂Cl₂ (600 μL) in an NMR tube. NMRspectra were acquired at 25° C. until the G1 had completely reacted asdetermined by the disappearance of its alkylidene α proton signal.Cyclohex-3-enecarbaldehyde 9 (52.7 mg, 0.48 mmol) was added to the NMRtube. When no further propagation occurred, the reaction was quenchedwith ethyl vinyl ether and stirred for 30 min. The solvent wasevaporated, and the alternating copolymer was purified by chromatographyon silica gel (97:3/CH₂Cl₂:acetone). ¹H NMR (500 MHz, CD₂Cl₂): δ 9.59(m, 27H), 7.25 (m, 5H), 6.59 (m, 27H), 5.83 (m, 27H), 5.36 (m, 27H),4.39 (m, 54H), 3.59 (m, 54H), 3.0-1.25 (m, 560H). M_(n) ^(calc)=9700,M_(n) ^(GPC)=14823, M_(w) ^(GPC)=31649,

_(M)=2.13.

Post-Polymerization Modification

In the first step of post-polymerization modifications the bromide wasconverted to an azide by mixing poly(3-alt-4)_(n) and NaN₃ in DMF at 60°C. for 3 hours. Poly(3′-alt-4)_(n) was obtained after workup. ¹H NMR ofpoly(3′-alt-4)_(n) showed no significant difference from that ofpoly(3-alt-4)_(n), so were the GPC traces. Therefore, we obtained IRspectra which showed a distinctive N₃ vibration signal at around 2200cm⁻¹.

Poly(3′-alt-4)_(n). To a solution of poly(3-alt-4)_(n) (44.0 mg, 4.51μmol) in anhydrous DMF (1 mL) was added NaN₃ (23.0 mg, 353 μmol). Themixture was stirred at 60° C. for 3 h, and water (5 mL) was added andthe mixture was extracted with CH₂Cl₂ (3×5 mL). The combined organiclayers were washed with water and dried over MgSO₄. After filtration,the solvent was evaporated by vacuum to give a yellow oil (31.0 mg,80%). ¹H NMR (500 MHz, CD₃OD): δ 9.50 (m, 27H), 7.24 (m, 5H), 6.48 (m,27H), 5.78 (m, 27H), 5.30 (m, 27H), 4.20 (m, 59H), 3.50 (m, 59H),3.00-1.35 (m, 863H). IR (KBr): 3418, 2924, 2854, 2718, 2104, 1716, 1633cm⁻¹.

Poly(3′-alt-4-DH)_(n). Poly(3′-alt-4)_(n) (4.7 mg, 0.54 μmol) and dansylhydrazide (5.5 mg, 21 μmol) were dissolved in THF (2 mL). The mixturewas stirred at 65° C. for 2 h and the solution was concentrated undervacuum. The residue was purified by LH-20 with eluting solvent as THF.¹H NMR (400 MHz, CD₂Cl₂): δ 8.56 (bs, 47H), 8.42 (bs, 39H), 8.28 (bs,39H), 8.00 (bs, 47H), 7.54 (bs, 87H), 7.20 (bs, 96H), 6.43 (bs, 27H),5.68 (bs, 29H), 5.13 (bs, 31H), 4.30 (bs, 137H), 3.46 (bs, 131H), 2.94(bs, 155H), 2.88 (bs, 243H), 2.86 (s, 172H), 2.80-1.01 (m, 1618H). M_(n)^(calc)=16369, M_(n) ^(GPC)=19325, M_(w) ^(GPC)=34382,

_(M)=1.78.

Poly(3′-Trp-alt-4)_(n). Under an N₂ atmosphere, poly(3′-alt-4)_(n) (5.9mg, 0.67 μmol), Boc-Trp-alkyn (10.6 mg, 25.6 μmol), CuBr (1.7 mg, 0.20μmol) and PEDTA (6.7 μL) were mixed in THF (1 mL). After stirring for 12h, the solution was concentrated and the residue was purified by LH-20with eluting solvent as THF. M_(n) ^(calc)=16715, M_(n) ^(GPC)=12472,M_(w) ^(GPC)=20226,

_(M)=1.62.

Poly(3′-Trp-alt-4-DH)_(n). Under an N₂ atmosphere, poly(3′-alt-4). (7.0mg, 0.80 mmol), dansyl hydrazide (8.2 mg, 31 μmol), Boc-Trp-alkyn (12.5mg, 30.0 mmol), CuBr (2.0 mg, 0.24 mmol) and PEDTA (7.9 μL) were mixedin THF (1 mL). The mixture was stirred at 65° C. for 12 h, the solutionwas concentrated and the residue was purified by LH-20 with elutingsolvent as THF. M_(n) ^(calc)=22491, M_(n) ^(GPC)=21645, M_(w)^(GPC)=38312,

_(M)=1.747. IR (KBr): 3413, 2929, 2854, 1707, 1690 cm⁻¹.

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We claim:
 1. A method for producing a polymer comprising the repeatingunit (Ib) or (Ic):

which comprises contacting an olefin of structure (II) with acyclobutene of structure (III)

in the presence of an olefin metathesis catalyst, wherein R is selectedfrom the group consisting of H, C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₃-C₈cycloalkyl, heterocyclyl, aryl, C₁-C₂₀ alkoxy, C₁-C₂₀ alkenyloxy, C₃-C₆cycloalkyloxy, aryloxy, heterocyclyloxy, C₁-C₂₀ alkylamino, C₁-C₂₀alkenylamino, C₃-C₈ cycloalkylamino, heterocyclylamino, or arylamino andmay be optionally substituted with up to three substituents selectedfrom halo, CN, NO₂, oxo, alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl,aryl, and a heterocyclic group; n is a number between 2 and 20; R¹through R⁶ are independently selected from the group consisting of H,aldehyde, C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₃-C₆ cycloalkyl, aryl,heterocyclyl, C₁-C₂₀ alkoxy, C₁-C₂₀ acyloxy, C₂-C₂₀ alkenyloxy, C₃-C₆cycloalkyloxy, aryloxy, heterocyclyloxy, C₁-C₂₀ alkylamino, C₂-C₂₀alkenylamino, C₃-C₈ cycloalkylamino, heterocyclylamino, arylamino, orhalogen; R¹ through R⁶ may be taken together to form a 5- to 7-memberedring which may be optionally substituted with up to three substituentsselected from halo, CN, NO₂, oxo, alkyl, cycloalkyl, alkenyl, alkynyl,aralkyl, aryl, or a heterocyclic group; A is a C₂-C₂₀ alkyl; with theproviso that any carbon-carbon double bonds in R or in R¹ through R⁶ areessentially unreactive toward metathesis reactions with the catalyst. 2.The method of claim 1, further comprising combining a polymer blockcomprising repeating units (Ib) or (Ic) into a block copolymer.
 3. Themethod of claim 1, wherein the catalyst is an alkylidene rutheniumcomplex of formula (L)(L′)X₂Ru=CHR′ or (L)₂(L′)X₂Ru═CHR′, wherein R′ isselected from the group consisting of H, C₁-C₁₀ alkyl, C₂-C₁₀ alkenyl,C₃-C₆ cycloalkyl, and aryl; L is a ligand selected from the groupconsisting of trialkyl phosphines, triarylphosphines,tri(cycloalkyl)phosphines, pyridine and substituted pyridine; L′ is aligand selected from the group consisting of trialkyl phosphines,triarylphosphines, tri(cycloalkyl)phosphines, pyridine and substitutedpyridine, and imidazolin-2-ylidine carbenes of formula

wherein Ar is an ortho-substituted aryl or an aryl; and X is F, Cl, orBr.
 4. The method of claim 2, wherein the catalyst is an alkylideneruthenium complex of formula (L)(L′)X₂Ru═CHR′ or (L)₂(L′)X₂Ru═CHR′,wherein R′ is selected from the group consisting of H, C₁-C₁₀ alkyl,C₂-C₁₀ alkenyl, C₃-C₆ cycloalkyl, and aryl; L is a ligand selected fromthe group consisting of trialkyl phosphines, triarylphosphines,tri(cycloalkyl)phosphines, pyridine and substituted pyridine; L′ is aligand selected from the group consisting of trialkyl phosphines,triarylphosphines, tri(cycloalkyl)phosphines, pyridine and substitutedpyridine, and imidazolin-2-ylidine carbenes of formula

wherein Ar is an ortho-substituted aryl or an aryl; and X is F, Cl, orBr.
 5. The method of claim 3, wherein L is pyridine or substitutedpyridine.
 6. The method of claim 4, wherein L is 3-bromopyridyl,3-chloropyridyl or pyridine.
 7. The method of claim 3, wherein L′ is animidazolin-2-ylidine carbene and Ar is selected from the groupconsisting of phenyl, mesityl, 2-methylphenyl, 2-ethylphenyl,2-isopropylphenyl, 2,3-diisopropylphenyl, 2,6-difluorophenyl, and3,5-di-t-butylphenyl.
 8. The method of claim 1, wherein the catalyst isa molybdenum or tungsten metathesis catalyst.